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Study On The Expression And Correction Of Matrix Metalloproteinase-1, Timp-3 And Insulin-like Growth Factor-1 In Condyloma Acuminatum

Posted on:2011-10-09Degree:MasterType:Thesis
Country:ChinaCandidate:P Y TangFull Text:PDF
GTID:2194360308984985Subject:Dermatology and Venereology
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Background and Objectives:Condyloma acuminatum (CA), is one of the most common sexually transmitted disease (STD) and a typer of tumor cased by human papilloma virus (HPV). The incidence of CA is higher year by year, so the increasing attention has been paid.Matrix metallrotemase (MMPs) can degrade the basement membrane (BM) and the extracellular matrix (ECM) to promote tumor angiogenesis, playing an improtant role in the process of tumor growth.And TIMPs, with the function of inhibiting tumor aniogenesis, is the natural inhibitor of MMPs.IGF-1 has an effect on cell proliferation, differentiation and inhibits apoptosis, it can activate urokinase plasminogen activator-1 (uPA), to induce the expression of other ECM protease, such as MMP-9, playing an improtant role in the process of tumor aniogenesis.The growth and recurrence of CA is based on angiogenesis, so MMPs / TIMPs and IGF-1 may play the vital role in the process of CA.At present, the biological characteristics of MMPs / TIMPs have not yet been fully understood, so the research is still in the early stage. Furthermore, the expression of IGF-1 in CA has not yet been report at home and abroad. To explore the pathogenesis of CA, we studied on the expression and correlation of MMP-1, TIMP-3 and IGF-1 in CA.Methods:Collected 11 cases of CA tissues as the disease group and 5 cases of normal foreskin tissues as the control group, used Affymetrix HG U133 Plus 2.0 GeneChip to detect the differential genes expression between CA and normal foreskin. Validated the results of GeneChip with QuantiGene Plex 2.0 Reagent System.Expanded the number of samples to 34 cases of CA and 25 cases of normal foreskin, detected the expression of MMP-1, TIMP-3 and IGF-1 mRNA with QuantiGene Plex 2.0. There were independent-samples t test, Mann-Whitney U test and Spearman correlation analysis were used with SPSS 13.0 software to statistical analysis. Significance level isα= 0.05. Result:4,830 differential transcripts between CA and normal foreskin were found, including 2,426 were up-regulated and 2,404 were down-regulated. The result of verification with QuantiGene Plex 2.0 were consistent with the GeneChip, proved the result of GeneChip was accurate and reliable. In 34 cases of CA, 15 cases were HPV 6 infection (44.12%), 5 cases were HPV 11 infection (14.71%), 13 cases were HPV 6 / 11 infection (38.24%) and 1 case was HPV 11/66 infection (2.94%), it is not dectected the infection of HPV 16 and / or 18.The expression of MMP-1 mRNA in CA was higher than normal foreskin, the difference was statistically significant (t = 4.251, P <0.001). The expression of MMP-1 mRNA in male CA was higher than normal foreskin, the difference was statistically significant (Z=4.308, P<0.001). The expression of TIMP-3 and IGF-1 mRNA in CA were lower than normal foreskin, the difference were statistically significant (t = 10.796, 6.216, both P<0.001). The expression of TIMP-3 and IGF-1 mRNA in male CA were lower than normal foreskin, the difference were statistically significant (Z =5.851, 5.686, both P<0.001). In CA, it was not significant correlation about the expression of MMP-1 and TIMP-3, and MMP-1 and IGF-1 (rs = 0.104, 0.041, P = 0.559, 0.816). it was positively correlated about the expression of TIMP-3 and IGF-1 (rs = 0.747, P <0.001).Conclusion:The result of GeneChip was accurate and reliable and it can be used as a new method for screening differential gene expression. CA was mainly infected by HPV 6 and 11. The expression of MMP-1 mRNA is higher in CA, the expression of TIMP-3 and IGF-1 mRNA is lower in CA. In CA, TIMP-3 is not the major inhibitor of MMP-1, or there are other factors interfere the progress of TIMP-3 inhibit MMP-1. IFG-1 and TIMP-3 may have a synergistic effect in the pathogenesis of CA.
Keywords/Search Tags:HPV, condyloma accuminatum, MMP-1, TIMP-3, IGF-1
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